tbuckley/cabot-search huggingface dataset:
The COVID-19 pandemic and health-related quality of life across 13 high- and low-middle-income countries: A cross-sectional analysis
Authors: Mara Violato, Jack Pollard, Andrew Lloyd, Laurence S. J. Roope, Raymond Duch, Matias Fuentes Becerra, Philip M. Clarke
Journal: PLoS Medicine (2023)

Background Most research on the Coronavirus Disease 2019 (COVID-19) health burden has focused on confirmed cases and deaths, rather than consequences for the general population’s health-related quality of life (HRQoL). It is also important to consider HRQoL to better understand the potential multifaceted implications of the COVID-19 pandemic in various international contexts. This study aimed to assess the association between the COVID-19 pandemic and changes in HRQoL in 13 diverse countries. Methods and findings Adults (18+ years) were surveyed online (24 November to 17 December 2020) in 13 countries spanning 6 continents. Our cross-sectional study used descriptive and regression-based analyses (age adjusted and stratified by gender) to assess the association between the pandemic and changes in the general population’s HRQoL, measured by the EQ-5D-5L instrument and its domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and how overall health deterioration was associated with individual-level (socioeconomic, clinical, and experiences of COVID-19) and national-level (pandemic severity, government responsiveness, and effectiveness) factors. We also produced country-level quality-adjusted life years (QALYs) associated to COVID-19 pandemic-related morbidity. We found that overall health deteriorated, on average across countries, for more than one-third of the 15,480 participants, mostly in the anxiety/depression health domain, especially for younger people (&lt;35 years old) and females/other gender. This translated overall into a 0.066 mean “loss” (95% CI: −0.075, −0.057; p -value &lt; 0.001) in the EQ-5D-5L index, representing a reduction of 8% in overall HRQoL. QALYs lost associated with morbidity were 5 to 11 times greater than QALYs lost based on COVID-19 premature mortality. A limitation of the study is that participants were asked to complete the prepandemic health questionnaire retrospectively, meaning responses may be subject to recall bias. Conclusions In this study, we observed that the COVID-19 pandemic was associated with a reduction in perceived HRQoL globally, especially with respect to the anxiety/depression health domain and among younger people. The COVID-19 health burden would therefore be substantially underestimated if based only on mortality. HRQoL measures are important to fully capture morbidity from the pandemic in the general population.
Differences in Social Determinants of Health Underlie Racial/Ethnic Disparities in Psychological Health and Well-Being: Study of 11,143 Older Adults
Authors: Dylan J. Jester, Jordan N. Kohn, Lize Tibiriçá, Michael L. Thomas, Lauren L. Brown, James D. Murphy, Dilip V. Jeste
Journal: American Journal of Psychiatry (2023)

Objective: The authors sought to determine the impact of selected social determinants of health (SDoH) on psychological health and well-being (defined as depression, cognition, and self-rated health) among Black and Hispanic/Latinx adults relative to White adults 51–89 years of age. Methods: Disparities in depressive symptomatology, cognition, and self-rated health were measured among 2,306 non–Hispanic/Latinx Black, 1,593 Hispanic/Latinx, and 7,244 non–Hispanic/Latinx White adults who participated in the Health and Retirement Study (N=11,143). Blinder-Oaxaca decomposition was used to examine whether differences in selected SDoH explained a larger share of the disparities than age, sex, measures of health, health behaviors, and health care utilization. Selected SDoH included education, parental education, number of years worked, marital status, veteran status, geographic residence, nativity status, income, and insurance coverage. Results: Black and Hispanic/Latinx adults reported worse depressive symptomatology, cognition, and self-rated health than White adults. Selected SDoH were associated with a larger proportion of the Black–White disparities in depressive symptomatology (51%), cognition (39%), and self-rated health (37%) than were age, sex, measures of health, health behaviors, and health care utilization. SDoH were associated with a larger proportion of the Hispanic/Latinx–White disparity in cognition (76%) and self-rated health (75%), but age and physical health correlated with the disparity in depressive symptomatology (28%). Education, parental education, years worked, income, and insurance parity were SDoH associated with these disparities. Conclusions: Differences in SDoH underlie racial/ethnic disparities in depression, cognition, and self-rated health among older adults. Education, income, number of years worked, and insurance parity are key SDoH.
Sublingual Buprenorphine-Naloxone Exposure and Dental Disease
Authors: Dennis P. Watson, Sodabeh Etminan, Nicole Gastala
Journal: JAMA (2023)

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Irradiation stent with 125I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial
Authors: Jian Lu, Jin-He Guo, Jian-Song Ji, Yu-Liang Li, Wei-Fu Lv, Hai-Dong Zhu, Jun-Hui Sun, Wei-Xin Ren, Fu-Jun Zhang, Wei-Dong Wang, Hai-Bo Shao, Guang-Shao Cao, Hai-Liang Li, Kun Gao, Po Yang, Guo-Wen Yin, Guang-Yu Zhu, Fa-Zong Wu, Wu-Jie Wang, Dong Lu, Sheng-Qun Chen, Jie Min, Yang Zhao, Rui Li, Li-Gong Lu, Wan Yee Lau, Gao-Jun Teng
Journal: International Journal of Surgery (2023)

Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients.In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety.Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73).Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.
Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs
Authors: Johan Sundström, Lars Lind, Shamim Nowrouzi, Emil Hagström, Claes Held, Per Lytsy, Bruce Neal, Kerstin Marttala, Ollie Östlund
Journal: JAMA (2023)

Importance Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure–lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. Objective To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. Design, Setting, and Participants A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Interventions Each participant was scheduled for treatment in random order with 4 different classes of blood pressure–lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Main Outcomes and Measures Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. Results There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals ( P &amp;amp;lt; .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg–lower systolic blood pressure. Conclusions and Relevance These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. Trial Registration ClinicalTrials.gov Identifier: NCT02774460
In vivo screening identifies SPP2, a secreted factor that negatively regulates liver regeneration
Authors: Yu-Hsuan Lin, Qiyu Zeng, Yuemeng Jia, Zixi Wang, Lin Li, Meng-Hsiung Hsieh, Qiang Cheng, Chase A. Pagani, Nicholas Livingston, Jeon Lee, Yu Zhang, Tripti Sharma, Daniel J. Siegwart, Dean Yimlamai, Benjamin Levi, Hao Zhu
Journal: Hepatology (2023)

Background and Aims: The liver is remarkably regenerative and can completely recover even when 80% of its mass is surgically removed. Identification of secreted factors that regulate liver growth would help us understand how organ size and regeneration are controlled but also provide candidate targets to promote regeneration or impair cancer growth. Approach and Results: To enrich for secreted factors that regulate growth control, we induced massive liver overgrowth with either YAP or MYC . Differentially expressed secreted factors were identified in these livers using transcriptomic analysis. To rank candidates by functionality, we performed in vivo CRISPR screening using the Fah knockout model of tyrosinemia. We identified secreted phosphoprotein-2 (SPP2) as a secreted factor that negatively regulates regeneration. Spp2 -deficient mice showed increased survival after acetaminophen poisoning and reduced fibrosis after repeated carbon tetrachloride injections. We examined the impact of SPP2 on bone morphogenetic protein signaling in liver cells and found that SPP2 antagonized bone morphogenetic protein signaling in vitro and in vivo. We also identified cell-surface receptors that interact with SPP2 using a proximity biotinylation assay coupled with mass spectrometry. We showed that SPP2’s interactions with integrin family members are in part responsible for some of the regeneration phenotypes. Conclusions: Using an in vivo CRISPR screening system, we identified SPP2 as a secreted factor that negatively regulates liver regeneration. This study provides ways to identify, validate, and characterize secreted factors in vivo.
Suicide Around the Anniversary of a Parent’s Death in Sweden
Authors: Alessandra Grotta, Can Liu, Ayako Hiyoshi, Lisa Berg, Ichiro Kawachi, Jan Saarela, Mikael Rostila
Journal: JAMA Network Open (2023)

Importance Bereavement following parental death experienced in adulthood may be associated with suicide over many years, but this risk has received scant attention. Objective To investigate whether the risk of suicide increases among adult children around the anniversary of a parent’s death. Design, Setting, and Participants This case-crossover study used Swedish register-based longitudinal data from 1990 to 2016, based on the entire national population. Participants included all adults aged 18 to 65 years who experienced parental death and subsequently died by suicide. Conditional logistic regression was used to quantify the association between the anniversary (or preanniversary and postanniversary periods) and suicide, controlling for time-invariant confounding. All analyses were stratified by sex of the offspring. The analyses were also stratified by the sex of the deceased parent, time since parental death, age, and marital status. Data analyses were performed in June 2022. Exposures Anniversary of a parent’s death (or preanniversary and postanniversary periods). Main Outcomes and Measures Suicide. Results Of 7694 individuals who died by suicide (76% intentional self-harm), 2255 (29%) were women, and the median (IQR) age at suicide was 55 (47-62) years. There was evidence of an anniversary reaction among women, with a 67% increase in the odds of suicide when exposed to the period from the anniversary to 2 days after the anniversary, compared with when not being exposed (odds ratio [OR], 1.67; 95% CI, 1.07-2.62). The risk was particularly pronounced among maternally bereaved women (OR, 2.29; 95% CI, 1.20-4.40) and women who were never married (OR, 2.08; 95% CI, 0.99-4.37), although the latter was not statistically significant. An increased risk of suicide from the day before up to the anniversary was observed among women bereaved between the ages of 18 and 34 years (OR, 3.46; 95% CI, 1.14-10.56) and between the ages of 50 and 65 years (OR, 2.53; 95% CI, 1.04-6.15). Men had an attenuated suicide risk for the period from the day before up to the anniversary (OR, 0.57; 95% CI, 0.36-0.92). Conclusions and Relevance These findings suggest that the anniversary of a parent’s death is associated with an increased suicide risk among women. Women bereaved at younger or older ages, those who were maternally bereaved, and those who never married appeared to be particularly vulnerable. Families and social and health care professionals need to consider anniversary reactions in suicide prevention.
Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors
Authors: Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer
Journal: Neuro-Oncology (2023)

Abstract Background Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI. Methods Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency &amp;gt; 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P &amp;lt; 5 × 10−5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P &amp;lt; .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P &amp;lt; 5 × 10−8) in a meta-analysis across ancestry groups. Results Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at a median age of 8.3 years. Overall, 1150 neurocognitive evaluations were obtained (median = 5, range: 2–10 per participant). One of the five loci previously associated with cognitive outcomes in pediatric CNS tumors survivors demonstrated significant time-dependent IQ declines (PPARA rs6008197, P = .004). Two variants associated with IQ in the general population were associated with declines in IQ after Bonferroni correction (rs9348721, P = 1.7 × 10−5; rs31771, P = 7.8 × 10−4). In genome-wide analyses, we identified novel loci associated with accelerated declines in IQ (rs116595313, meta-P = 9.4 × 10−9), WM (rs17774009, meta-P = 4.2 × 10−9), and PS (rs77467524, meta-P = 1.5 × 10−8; rs17630683, meta-P = 2.0 × 10−8; rs73249323, meta-P = 3.1 × 10−8). Conclusions Inherited genetic variants involved in baseline cognitive functioning and novel susceptibility loci jointly influence the degree of treatment-associated cognitive decline in pediatric CNS tumor survivors.
Evolution of the SARS-CoV-2 Mutational Spectrum
Authors: Jesse D Bloom, Annabel C Beichman, Richard A Neher, Kelley Harris
Journal: Molecular Biology and Evolution (2023)

Abstract SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.
Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies
Authors: Bernard A. Fox, Walter J. Urba, Shawn M. Jensen, David B. Page, Brendan D. Curti, Rachel E. Sanborn, Rom S. Leidner
Journal: Clinical Cancer Research (2023)

Summary The authors of a recent study identified noncanonical peptides (NCP) presented by cancer cells’ HLA and observed lack of reactivity to these antigens by endogenous tumor-reactive T cells. In vitro sensitization generated NCP-reactive T cells that recognized epitopes shared by a majority of cancers tested, providing opportunities for novel therapies to shared antigens. See related article by Lozano-Rabella et al., p. 2250
Diagnosis and Management of Prediabetes
Authors: Justin B. Echouffo-Tcheugui, Leigh Perreault, Linong Ji, Sam Dagogo-Jack
Journal: JAMA (2023)

Importance Prediabetes, an intermediate stage between normal glucose regulation and diabetes, affects 1 in 3 adults in the US and approximately 720 million individuals worldwide. Observations Prediabetes is defined by a fasting glucose level of 100 to 125 mg/dL, a glucose level of 140 to 199 mg/dL measured 2 hours after a 75-g oral glucose load, or glycated hemoglobin level (HbA 1C ) of 5.7% to 6.4% or 6.0% to 6.4%. In the US, approximately 10% of people with prediabetes progress to having diabetes each year. A meta-analysis found that prediabetes at baseline was associated with increased mortality and increased cardiovascular event rates (excess absolute risk, 7.36 per 10 000 person-years for mortality and 8.75 per 10 000 person-years for cardiovascular disease during 6.6 years). Intensive lifestyle modification, consisting of calorie restriction, increased physical activity (≥150 min/wk), self-monitoring, and motivational support, decreased the incidence of diabetes by 6.2 cases per 100 person-years during a 3-year period. Metformin decreased the risk of diabetes among individuals with prediabetes by 3.2 cases per 100 person-years during 3 years. Metformin is most effective for women with prior gestational diabetes and for individuals younger than 60 years with body mass index of 35 or greater, fasting plasma glucose level of 110 mg/dL or higher, or HbA 1c level of 6.0% or higher. Conclusions and Relevance Prediabetes is associated with increased risk of diabetes, cardiovascular events, and mortality. First-line therapy for prediabetes is lifestyle modification that includes weight loss and exercise or metformin. Lifestyle modification is associated with a larger benefit than metformin.
Innovative Design Strategies Advance Biomedical Applications of Phthalocyanines
Authors: Dong Li, Shundong Cai, Peiyu Wang, Hongwei Cheng, Bingwei Cheng, Yang Zhang, Gang Liu
Journal: Advanced Healthcare Materials (2023)

Owing to their long absorption wavelengths, high molar absorptivity, and tunable photosensitivity, phthalocyanines have been widely used in photodynamic therapy (PDT). However, phthalocyanines still face the drawbacks of poor targeting, "always-on" photosensitizing properties, and unsatisfactory therapeutic efficiency, which limit their wide applications in biomedical fields. Thus, new design strategies such as modification of targeting molecules, formation of nanoparticles, and activating photosensitizers are developed to improve the above defects. Notably, recent studies have shown that novel phthalocyanines are not only used in fluorescence imaging and PDT, but also in photoacoustic imaging, photothermal imaging, sonodynamic therapy, and photothermal therapy. This review focuses on recent design strategies, applications in biomedicine, and clinical development of phthalocyanines, providing ideas and references for the design and application of phthalocyanine, so as to promote their future transformation into clinical applications.